Fighting Antibiotic-Resistant Superbugs With Marine Microorganisms

Chemists reported in the journal Angewandte Chemie that they reproduced a marine compound that inhibits the growth of antibiotic-resistant bacteria, or “superbugs.”

A microorganism found off the coast of Alicante shows promise for fighting the growing superbug problem. Chemists at the Combinatorial Lab were able to synthesize baringolin and reveal its structure, opening up the possibility to better understand more about these microorganisms’ antibiotic properties.

“This substance has 128 possible structural configurations but only one is an exact replica of the natural peptide. We have been able to find it via 39 synthesis steps,” said Xavier Just-Baringo, who is doing his PhD in the Combinatorial Chemistry Lab.

The researchers finely tuned the organic synthesis of the natural peptide and several analogues, and they plan to attempt to improve the molecules’ pharmacological and pharmacokinetic properties. The molecules are a new family of antibacterial agents of terrestrial and marine origin, and about 100 have been identified to date.

“There is only one thiopeptide on the market for the treatment of bacterial infections, thiostrepton (Panolog), and it is used in veterinary medicine for skin infections. Nothing is available for humans yet,” explains Mercedes Ãlvarez, associate researcher in the lab, senior professor at the University of Barcelona (UB), and supervisor of the study.

In order for baringolin to be a viable drug, its solubility must be improved because antibiotics are administered orally or intravenously.

“Using the analogues, we aim to improve this feature and identify the parts of the molecule responsible for their antibiotic activity in order to be able to design new more active and smaller analogues,” says Ãlvarez.

Fernando Albericio, who heads the Combinatorial Lab, said they have taken the first step towards achieving a future drug, learning how to synthesize natural molecules and develop new methods. The final step for the lab is to achieve the total synthesis of natural substances.

“The synthesis of natural products in the lab has a double justification. One is environmental, to protect species that hold substances of pharmacological interest, and the other is commercial, as manufacturing a drug on a large scale is viable only if its production can be ensured on an industrial scale,” the researchers wrote in the journal.

Antibiotic-resistant bacteria are becoming a growing health threat; so much so that Britain’s top health official said in March that it would like to add these superbugs to the list. A new study released in Science Translational Medicine found that low doses of silver could make bacteria more susceptible to antibiotic attack.